1. Field of the Invention
The present invention relates generally to facilitating release of powder contained in a receptacle. More specifically, the present invention relates to the administration of medication by a method and apparatus for facilitating inhalation of powder medicaments.
2. Related Art
In the medical field, it is often desirable to administer various forms of medication to patients. Well known methods of introducing medication into the human body include the oral ingestion of capsules and tablets, intravenous injection through hypodermic needles, and numerous others. In one method, certain medications may be inhaled into a patient""s respiratory tract and lungs through the nose or mouth. Certain of these medications, such as bronchodilators, corticosteroids, etc., for the treatment of asthma and other respiratory anomalies, may be aimed at the respiratory tract directly. Others are inhaled for purposes of systemic treatment, i.e. for treatment of any area of the body through absorption from the respiratory tract through the lung tissue, into the deep lungs, and into the bloodstream. Each of these medications comes in a variety of forms, including fluids, which are commonly administered as an aerosol vapor or mist, as well as solids. Inhalable solids typically take the form of fine, dry powders. Specialized devices, such as inhalers, are provided to assist the patient in directing these fine powder medications into the respiratory tract.
Various types of inhalers are known for the administration of dry powder medicaments. However, each of these inhalers suffers certain drawbacks. For example, U.S. Pat. No. 5,787,881 discloses an inhaler that is used with encapsulated dry powder medicaments. However, use of this device requires numerous steps and imposes a number of inconveniences on a user. For example, the medication capsules used with the device have an aperture formed therein prior to insertion into an opening in the inhaler. Therefore, there exists a danger that an amount of medication may be lost prior to or during insertion into the device. After insertion of the capsule, use of the device requires the additional step that a cover must be closed before the medication may be inhaled.
Inhalation devices configured for use with a capsule containing some type of medicament are shown in U.S. Pat. No. 4,069,819 to Valentini et al. (xe2x80x9cthe ""819 patentxe2x80x9d) and U.S. Pat. No. 4,995,385 to Valentini et al. (xe2x80x9cthe ""385 patentxe2x80x9d). The inhalation device described in the ""385 patent was developed to overcome the drawbacks of the device described in the ""819 patent. Particularly, in a large number of cases, the device described in the ""819 patent experienced irregular and incomplete emptying of the capsule, thereby resulting in difficulties in properly administering the medicament in the capsule. The inhalation device described in the ""385 patent attempts to overcome this deficiency by tapering the nebulization chamber toward the end surface that comprises the discharge holes. Thus, the nebulization chamber of the ""385 patent is not cylindrical, but rather frusto-conical in form in an attempt to achieve regular complete emptying of the nebulization chamber.
However, further improvements in the design of inhalation devices are needed to achieve high emitted doses and highly dispersed powders while maintaining low resistance, especially when the inhaler is used with high doses and is operated at low peak inspiratory flow rates (PIFR) and low inhalation volumes. As used herein, xe2x80x9cemitted dosexe2x80x9d (ED) refers to the percentage of the dose of powder medicament that is emitted from a receptacle in the inhalation device. The dispersal of the powder can be quantified by measuring the volume mean geometric diameter (VMGD) of the emitted powder. As used herein xe2x80x9cvolume mean geometric diameterxe2x80x9d refers to the average geometric diameter of the powder. As used herein, xe2x80x9cresistancexe2x80x9d refers to the square root of the pressure gradient across the inhaler divided by the peak inspiratory flow rate through the inhaler. As used herein xe2x80x9clow peak inspiratory flow ratexe2x80x9d refers to a peak inspiratory flow rate of approximately 25 L/min or less. Moreover, improvements are needed to achieve high emitted doses and highly dispersed powders that are consistently reproducible, i.e., that have a low standard deviation of emitted dose percentage and VMGD, respectively.
Another drawback of the inhalation devices described in the ""819 and the ""385 patents is the piercing device that is used to puncture the capsule. Such conventional piercing devices are formed from circular stock, with the points created by pinching the stock at an angle, thereby creating a single sharp cutting edge. Drawbacks of such a design are that the point (which must puncture the capsule material) is often rounded, lessening its effectiveness as a piercing device. Moreover, burrs often form on the lower edge, which can stop the piercing device from retracting from the capsule, thereby causing a device failure. The holes formed by such a conventional piercing device are generally round, and do not have the appearance of being cut by a sharp edge. With such a conventional design, the capsule is often crushed, rather than punctured or pierced. If such a conventional piercing device is used with brittle capsule materials such as gelatin, pieces of capsule material of a size that can be inhaled are usually broken off from the capsule. Thus, conventional piercing devices are less than optimal, particularly for brittle capsule material.
Another drawback of conventional inhalation devices is that they have no means for indicating when the powder in the inhaler is ready for inhalation by the user. It is desirable to have a means for indicating to the user that a dose of powder is ready for inhalation. For example, it would be desirable for a patient using a device for dispensing fluticasone propionate (used to treat asthma) to know when the device is ready for inhalation.
Thus, there is a need in the art for an improved method and apparatus for inhalation of dry powder medicaments. What is needed is an inhaler that provides for a higher emitted dose that is consistently reproducible with low standard deviation. Such a need is particularly acute for low peak inspiratory flow rates, and for high dosage ranges. There is a further need in the art for an improved means for puncturing the capsule containing the medicament. The present invention, the description of which is fully set forth below, solves the need in the art for such improved methods and apparatus.
The present invention relates to a method and apparatus for facilitating release of powder from a device. In one aspect of the invention, a device for emitting powder is provided. The device includes a first casing portion, and a second casing portion removably coupled to the first casing portion. A cylindrical chamber, defined by a straight wall of circular cross section, is coupled to the first casing portion. The chamber has a proximal end and a distal end. A ring is circumferentially coupled to an inner surface of the chamber. The ring is preferably disposed at approximately a midpoint of the chamber, or, alternatively, disposed adjacent the proximal end of the chamber. The second casing portion includes an emitter portion disposed at the proximal end of the chamber when the first and second casing portions are coupled together. The emitter portion defines at least one aperture configured to emit powder therethrough.
In another aspect of the present invention, the device is configured as an inhalation device for administering powder. In this aspect of the present invention, the emitter portion is configured as an inhalation portion so that powder is dispersed in the chamber and administered to a user through the inhalation portion. The inhalation portion may be configured as a mouth piece for inhalation through the mouth, or as a nose piece for inhalation through the nose.
One aspect of the invention comprises an optimized configuration of a device for administering powder that comprises a chamber defined by a wall and configured to hold a receptacle containing a powder, the wall defining a plurality of vents, and the inhalation device further comprising an inhalation portion defining at least one aperture for emitting powder therethrough. The inhalation device is configured to have a resistance of at most 0.28 (cm H2O)1/2/L/min and to provide an emitted dose of at least 85% when the dose of powder is up to 20 mg and when the device is operated at a peak inspiratory flow rate of 25 L/min or less and at an inhalation volume of 0.75 L or less. Preferably the standard deviation of the emitted dose is 10% or less.
In another aspect, the device of the present invention is configured to cause the emitted powder to be highly dispersed. By xe2x80x9chighly dispersedxe2x80x9d is meant that the VMGD of the emitted powder is substantially similar to the VMGD of the powder contained in the receptacle. Highly dispersible powders have a low tendency to agglomerate, aggregate or clump together and/or, if agglomerated, aggregated or clumped together, are easily dispersed or de-agglomerated as they emit from an inhaler and are breathed in by the subject. Typically, the highly dispersible particles suitable in the methods of the invention display very low aggregation compared to standard micronized powders which have similar aerodynamic diameters and which are suitable for delivery to the pulmonary system. Properties that enhance dispersibility include, for example, particle charge, surface roughness, surface chemistry, relatively large geometric diameters, and the configuration of the device used to dispense the powder.
In another aspect of the invention, the powder is contained in a receptacle that is disposed in the chamber. Upon puncturing the receptacle, powder is dispersed in the chamber and emitted or inhaled from the device.
In yet another aspect of the present invention, the device of the present invention includes means for puncturing the receptacle. In one embodiment, the means for puncturing can be configured as a staple. Such a staple is preferably configured in a substantially U-shape, having two prongs. In one aspect of the present invention, each of the prongs has a square cross-section. In another aspect of the present invention, the substantially U-shaped staple includes a rounded portion and two prongs that define a non-planar inner edge and a non-planar outer edge of the staple, the staple being formed from a rectangular length having two end surfaces and four planar side surfaces that intersect to form four non-planar edges. The inner edge of the staple is configured to be one of the non-planar edges, and the outer edge of the staple is the non-planar edge that is opposite that non-planar edge. Each end surface is an angled diamond-shaped surface. In a preferred aspect, each end surface has a top point at an apex of the inner edge, and a bottom point at an apex of the outer edge, each top point forming a cutting point for one of the prongs.
In another embodiment, the puncturing means can be configured as a substantially longitudinal prong comprising a puncturing surface on the distal end of the prong, a primary cutting surface running from the proximal end to the distal end of the prong and terminating at the puncturing surface, and a substantially planar face opposite to the primary cutting edge and running from the proximal end to the distal end of the prong. Another embodiment of the puncturing means comprises a substantially longitudinal prong comprising a puncturing surface on the distal end, a primary cutting surface terminating at the puncturing surface, and a face opposite to the primary cutting edge, wherein the prong is configured to create an opening in a wall by forming a hanging chad in the wall, the hanging chad having a free end formed by the puncturing surface and the primary cutting edge and a hinge coupled to the wall formed by the face. In another embodiment, the prong is configured to form a hanging chad in a wall of the receptacle having a longitudinal axis substantially parallel to the prong and a minor axis substantially perpendicular to the longitudinal axis, the hanging chad being opened to an angle of at least 30 to 45 degrees with respect to the minor axis of the receptacle. In another embodiment the prong is configured so that at least xc2xe of the length of the prong can be inserted into a receptacle without breaking off chads in the receptacle.
In each of these embodiments, the prong preferably has an angled surface at the distal end, the surface having a distal end terminating at the puncturing surface and a proximal end terminating at the substantially planar face. In addition, the prong preferably is tapered, so that its distal end is smaller than its proximal end, to facilitate removing the prong from the receptacle. The prong also preferably has a plurality of longitudinal faces and a plurality of longitudinal edges running from the proximal end to the distal end of the prong. In one embodiment, the cross section of the prong is a pentagon. In a related embodiment, the width of the substantially planar face may be very small and the four longitudinal faces may be substantially at right angles to each other so that the prong has substantially a diamond shaped cross section. In another embodiment, the cross section of the prong is a triangle.
In another embodiment of the invention, the puncturing means comprises one or more of the longitudinal prongs coupled to a base, preferably in a U-shape. In another aspect of the invention, any of these embodiments of the longitudinal prongs may be coupled to the device for administering powder.
In still a further aspect of the present invention, a method for dispensing powder by inhalation is provided. Such a method comprises
providing a powder inhalation device, the device comprising
a first casing portion,
a cylindrical chamber, defined by a straight wall of circular cross-section, coupled to said first casing portion, said chamber having a proximal end and a distal end and configured to receive a receptacle therein, said chamber comprising a ring circumferentially coupled to an inner surface of said chamber, and
a second casing portion removably coupled to said first casing portion, said second casing portion comprising an inhalation portion disposed at the proximal end of said chamber when said first and said second casing portions are coupled, said inhalation portion comprising a hemispheric region defining a plurality of apertures configured to emit powder therethrough;
puncturing the receptacle to allow release of powder into said chamber; and
dispersing powder through inhalation of the powder through said inhalation portion.
In one aspect of the present invention, the inhaling step is carried out by inhaling the powder through a mouthpiece into a user""s mouth. Alternatively, the inhaling step may be carried out by inhaling the powder through a nose piece into a user""s nose.
The present invention also encompasses an indicating device comprising a body disposed within a casing and reversibly moveable between a first and a second position, an indicator moveable between a rest position and an indicating position, and a means for coupling the body and the indicator, wherein upon a first movement of the body from the first position to the second position, the means for coupling couples the body and the indicator, and upon a second movement of the body from the second position to the first position, the indicator moves from the rest position to the indicating position.
In another embodiment, the present invention encompasses an indicating device comprising a body disposed within a casing and reversibly moveable between a first position and a second position, an indicator reversibly moveable between a rest position and an indicating position, a lip coupled to the indicator and a flange coupled to the body for engaging the lip, wherein upon a first movement of the body from the first position to the second position, the flange engages the lip, and upon a second movement of the body from the second position to the first position, the engagement of the lip and the flange causes the indicator to move from the rest position to the indicating position.
The invention further encompasses one of the previously described embodiments of a device for emitting powder comprising a means for indicating readiness of the device for emitting powder. The means for indicating readiness of the device for emitting powder may comprise one of the previously described embodiments of an indicating device.
In addition, the invention comprises a method for indicating the readiness of a device for emitting a medicament. Such a method comprises
providing a device for dispensing a medicament, the device comprising a casing comprising at least one aperture configured to emit powder therethrough, a body coupled to said casing and reversibly moveable between a first position and a second position, and an indicator coupled to said casing and reversibly moveable between a rest position and an indicating position;
applying an axial force to said body to move said body from said first position to said second position, which readies the powder for dispensing and couples said body to said indicator;
releasing said axial force from said body to allow said body to move from said second position to said first position, which moves said indicator to said indicating position; and
dispensing the medicament from said device.
The invention further comprises a method for indicating that a device for dispensing a medicament has been used. Such a method comprises
providing a device for dispensing a medicament, the device comprising a casing comprising at least one aperture configured to emit a medicament therethrough, a body coupled to said casing and reversibly moveable between a first position and a second position, and an indicator coupled to said casing and reversibly moveable between a rest position and an indicating position;
applying an axial force to said body to move said body from said first position to said second position, which couples said body to said indicator;
dispensing the medicament from the device;
releasing said axial force from said body to allow said body to move from said second position to said first position, which moves said indicator to said indicating position to indicate that the device has been used.
Features and Advantages
One feature of the present invention is that it provides, in a low resistance inhaler with a highly dispersed powder, high emitted doses that are consistently reproducible over a range of peak inspiratory flow rates, inhalation volumes and dosage quantities. Advantageously, the present invention improves and optimizes the emitted dose at low peak inspiratory flow rates, low inhalation volumes, and high dose ranges. A particularly advantageous feature of the present invention is its ability to operate at low peak inspiratory flow rates, such as would be associated with a child, an elderly person, or a person with a respiratory disease, such as chronic obstructive pulmonary disease (COPD).
One advantage of the present invention is that the means for puncturing used in the device is less expensive to manufacture than conventional piercing devices. Advantages of the injection molding manufacturing process used for the puncturing means include reliability, reproducibility, and design flexibility, such as the ability to make a wide variety of shapes and sizes of longitudinal prongs. For example, larger longitudinal prongs of the present invention can create larger openings in the receptacles than conventional piercing devices, which allows for higher emitted doses at low peak inspiratory flow rates, low volumes, and high dosage quantities. Another advantage of the present invention is that at least one configuration of the puncturing means facilitates forming a hanging chad in the wall of the receptacle, with an opening of at least 30 to 45 degrees, to facilitate more efficient removal of powder from the receptacle and, thus, higher emitted doses than could be achieved with conventional piercing devices. Moreover, the means for puncturing of the present invention advantageously provides improved puncturing performance since less force is needed to puncture the receptacles, and fewer failures result than with conventional piercing devices. Yet another advantage is that the prongs are shaped for easy removal from the receptacle without breaking off the hanging chad formed in the wall of the receptacle.
Another advantage of the preferred means for puncturing is an improvement to the emitted dose rate of the inhaler. In one aspect of the invention, the puncturing means improves the powder flow from the receptacle by increasing the size of the holes in the receptacle. In another aspect of the invention, the puncturing means improves the peak inspiratory flow rate by opening a hanging chad in the wall of the receptacle to an angle of at least 30 to 45 degrees with respect to the wall of the receptacle. Consequently, the emitted dose of the powdered medicament delivered to a patient will be independent of how fast the patient breathes, thereby ensuring that a consistent dose of medicament is delivered each time. Another advantageous feature of the present invention is the accuracy of medicament dosage delivered thereby. Since only one dosage of medication is present in the inhaler during each use, the possibility of overdose is eliminated, and the medicament need not be metered prior to delivery. A patient may simply inhale all medicament present in the device. Yet another advantage is the design of the puncturing means allows for a greater range of puncturing depths without breaking off the chads formed in the receptacle, allowing for greater optimization of the inhaler.
Because the present invention operates only under the inhalative power of the patient, the inhaler carries the additional advantage that no accessory device, such as a compressed air cylinder or other propellant, needs to be used in conjunction with the present invention.
Another advantage of the present invention is that during inhalation, the medicament is subjected to mixing in the dispersion chamber. This helps to ensure that the medicament exiting the inhaler and entering the patient""s respiratory system is in the form of a fine dry powder, facilitating medicament deposition in the lungs. In addition, inhalation of finer powders is typically more comfortable for the patient.
Still another advantage of the present invention is that it can be used with individuals who cannot breathe hard, such as a child, an elderly person, or a person suffering from a respiratory disease, such as asthma, or individuals who are sleeping or in a coma.
Yet another advantage of the apparatus of the present invention is that it is reusable. To reuse, a patient removes the emptied receptacle, and replaces it with a fresh receptacle filled with the proper dose of medicament.
Another advantage of the present invention is that it includes a means for indicating when a device for emitting powder is ready for inhalation. Such a means for indicating informs the user when the device is ready for use and/or when the device needs to be refilled or discarded. For example, the means for indicating could be used with a device for emitting fluticasone propionate (used to treat asthma) to indicate that the device is ready for inhalation. Alternatively, the means for indicating could be used with an epinephrine pen for treating allergies to indicate that the pen has been used. In addition, the means for indicating preferably makes an audible click so that a user will know when the device has been properly actuated. Also, the means for indicating is easy to manufacture and use.